-- Researchers in the United States say that cyclin-dependent kinase inhibitors may be an effective treatment for patients with HIV related kidney dysfunction
"The glomerular lesions of HIV-associated nephropathy (HIVAN) are associated with the expression of HIV-1 in podocytes," explained Dr. Peter J. Nelson and colleagues at Mount Sinai School of Medicine in New York City.
Cyclin-dependent kinase inhibitors reduced HIV expression by podocytes in vitro, Nelson and coauthors found.
The researchers added flavopiridol or roscovitine, which block the activity of cyclin-dependent kinase-9, to cultures of podocytes. Both drugs blocked HIV transcription in these cells, they said.
Roscovitine was more effective at preventing podocyte proliferation than flavopiridol, study data showed. However, flavopiridol had a lower inhibitory concentration than its counterpart, with an IC50 of 25 nM compared with the 3 µM IC50 roscovitine.
Both agents enabled the expression of podocyte differentiation markers, which had been suppressed by HIV gene expression (Suppression of HIV-1 expression by inhibitors of cyclin-dependent kinases promotes differentiation of infected podocytes, J Am Soc Nephrol 2001 Dec;12(12):2827-31.
"These results suggest that inhibition of HIV-1 transcription decreases podocyte proliferation and permits the reexpression of differentiation markers," Nelson and coworkers concluded. "Thus, suppression of HIV-1 transcription by selective cyclin-dependent kinase-9 inhibitors may be a useful therapeutic strategy for the treatment of HIVAN."
The corresponding author for this report is Dr. Peter Nelson, Division of Nephrology, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, Box 1243, New York, NY 10029, USA. E-mail: firstname.lastname@example.org.
Key points reported in this study include
- Cyclin-dependent kinase inhibitors reduce HIV expression by infected podocytes
- Suppression of HIV expression enabled the reexpression of podocyte differentiation markers
- These agents may be an effective treatment for HIV associated nephropathy
This article was prepared by AIDS Weekly editors from staff and other reports.